Increased glucose metabolic activity is associated with CD4+ T-cell activation and depletion during chronic HIV infection

Palmer, Clovis S.a; Ostrowski, Matiasb; Gouillou, Maelennc; Tsai, Louisd; Yu, Did; Zhou, Jinglinga; Henstridge, Darren C.e; Maisa, Annaa; Hearps, Anna C.a,f; Lewin, Sharon R.a,f,g; Landay, Alanh; Jaworowski, Anthonya,f; McCune, Joseph M.i; Crowe, Suzanne M.a,f,g

AIDS:
doi: 10.1097/QAD.0000000000000128
Basic Science
Abstract

Objectives: Glucose metabolism plays a fundamental role in supporting the growth, proliferation and effector functions of T cells. We investigated the impact of HIV infection on key processes that regulate glucose uptake and metabolism in primary CD4+ and CD8+ T cells.

Design and methods: Thirty-eight HIV-infected treatment-naive, 35 HIV+/combination antiretroviral therapy, seven HIV+ long-term nonprogressors and 25 HIV control individuals were studied. Basal markers of glycolysis [e.g. glucose transporter-1 (Glut1) expression, glucose uptake, intracellular glucose-6-phosphate, and L-lactate] were measured in T cells. The cellular markers of immune activation, CD38 and HLA-DR, were measured by flow cytometry.

Results: The surface expression of the Glut1 is up-regulated in CD4+ T cells in HIV-infected patients compared with uninfected controls. The percentage of circulating CD4+Glut1+ T cells was significantly increased in HIV-infected patients and was not restored to normal levels following combination antiretroviral therapy. Basal markers of glycolysis were significantly higher in CD4+Glut1+ T cells compared to CD4+Glut1 T cells. The proportion of CD4+Glut1+ T cells correlated positively with the expression of the cellular activation marker, HLA-DR, on total CD4+ T cells, but inversely with the absolute CD4+ T-cell count irrespective of HIV treatment status.

Conclusion: Our data suggest that Glut1 is a potentially novel and functional marker of CD4+ T-cell activation during HIV infection. In addition, Glut1 expression on CD4+ T cells may be exploited as a prognostic marker for CD4+ T-cell loss during HIV disease progression.

Author Information

aCentre for Biomedical Research, Burnet Institute, Melbourne, Australia

bInstituto de Investigaciones Biomédicas en Retrovirus y SIDA. Facultad de Medicina, Buenos Aires, Argentina

cCentre for Population Health, Burnet Institute, Melbourne

dLaboratory of Molecular Immunomodulation, School of Biomedical Sciences, Monash University, Clayton

eCellular and Molecular Metabolism Laboratory, Baker IDI Heart and Diabetes Institute

fDepartment of Infectious Diseases, Monash University

gInfectious Diseases Department, The Alfred hospital, Melbourne, Australia

hDepartment of Immunology/Microbiology, Rush University Medical Center, Chicago, Illinois

iDivision of Experimental Medicine, Department of Medicine, University of California, San Francisco, San Francisco, California, USA.

Correspondence to Clovis Palmer, Centre for Biomedical Research, Burnet Institute, 85 Commercial Road, Melbourne, VIC 3004, Australia. Tel: +61 3 8506 2389; e-mail: cpalmer@burnet.edu.au

Received 26 August, 2013

Revised 24 October, 2013

Accepted 24 October, 2013

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